Aralia elata inhibits neurodegeneration by downregulating O-GlcNAcylation of NF-κB in diabetic mice

• Published in: International journal of ophthalmology Vol. 10; no. 8; pp. 1203 - 1211
• Main Authors: Kim, Seong-Jae, Kim, Min-Jun, Choi, Mee-Young, Kim, Yoon-Sook, Yoo, Ji-Myong, Hong, Eun-Kyung, Ju, Sunmi, Choi, Wan-Sung
• Format: Journal Article
• Language: English
• Published: China International Journal of Ophthalmology Press 18-08-2017; Press of International Journal of Ophthalmology (IJO PRESS)
• Subjects: 1211; Aralia elata; Basic Research; diabetic retinopathy; mice; neurodegeneration; nuclear factor-kappa B; O-GlcNAc; O-GlcNAc transferase; Aralia elata; O-GlcNAc transferase; neurodegeneration; nuclear factor-kappa B; diabetic retinopathy; O-GlcNAc; mice
• ISSN: 2222-3959; 2227-4898
• DOI: 10.18240/ijo.2017.08.03

To investigate the role of O-GlcNAcylation of nuclear factor-kappa B (NF-κB) in retinal ganglion cell (RGC) death and analysedthe effect of
(AE) on neurodegeneration in diabetic mice.
C57BL/6mice with streptozotocin-induced diabetes were fed daily with AE extract or control (CTL) diet at the onset of diabetes mellitus (DM). Two months after injection of streptozotocin or saline, the degree of cell death and the expression of O-GlcNAc transferase (OGT), N-acetyl-b-D-glucosaminidase (OGA), O-GlcNAcylated proteins, and O-GlcNAcylation of NF-κB were examined.
AE did not affect the metabolic status of diabetic mice. The decrease in the inner retinal thickness (
<0.001
CTL,
<0.01
DM) and increases in RGCs with terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (
<0.001
CTL,
<0.0001
DM), glial activation, and active caspase-3 (
<0.0001
CTL,
<0.0001
DM) were blocked in diabetic retinas of AE extract-fed mice. Expression levels of protein O-GlcNAcylation and OGT were increased in diabetic retinas (
<0.0001
CTL), and the level of O-GlcNAcylation of the NF-κB p65 subunit was higher in diabetic retinas than in controls (
<0.0001
CTL). AE extract downregulated O-GlcNAcylation of NF-κB and prevented neurodegeneration induced by hyperglycemia (
<0.0001
DM).
O-GlcNAcylation of NF-κB is concerned in neuronal degeneration and that AE prevents diabetes-induced RGC apoptosis
downregulation of NF-κB O-GlcNAcylation. Hence, O-GlcNAcylation may be a new object for the treatment of DR, and AE may have therapeutic possibility to prevent diabetes-induced neurodegeneration.